INTRODUCTION:Memory complaints are common in individuals with epilepsy and often occur despite preserved performance on standard neuropsychological tests, indicating that subjective memory complaints (SMCs) may be influenced by cognitive and affective factors beyond objective memory impairment. We examined the associations between subjective memory appraisal, defined as patients' self-evaluative judgment of their memory function, and psychiatric, neurodevelopmental, and clinical variables, to identify factors linked to low subjective memory evaluation, a construct conceptually related to SMCs. METHODS:Subjective memory was assessed in 184 adults with epilepsy using a self-report questionnaire to evaluate overall quality of life, global memory function and common memory experiences. The items were rated on an 11-point Likert scale (0-10). Associations between subjective ratings and objective neuropsychological performance, psychiatric measures, neurodevelopmental traits, and clinical variables were examined. RESULTS:Exploratory factor analysis identified a single dominant factor accounting for 53.5 % of the variance, reflecting the global subjective memory appraisal (GSMA). GSMA showed a moderate negative correlation with depressive symptoms (Beck Depression Inventory-II [BDI-II]: r =  - 0.412, p < 0.001) and was associated with attention-deficit/hyperactivity disorder (ADHD)-related traits, particularly inattention (Conners' Adult ADHD Rating Scale [CAARS-A]: r =  - 0.536, p < 0.001). Associations with objective memory performance were weak. The core epilepsy-related variables showed little or no association with subjective memory perception. CONCLUSIONS:SMCs in epilepsy appear more closely tied to affective and attentional processes than to objective memory impairment or epilepsy severity. Incorporation of psychiatric and neurodevelopmental perspectives into clinical assessment may improve evaluation and management.

Objective: The clinical course of interictal psychosis (IIP) has not yet been investigated. We aimed to compared the psychopathology and time-relevant indices between chronic IIP (CIIP) and schizophrenia (SC) Methods: In this comprehensive psychopathological study, patients with chronic psychosis with and without epilepsy (127 with CIIP and 187 with SC) were compared. Psychopathology was measured using the Brief Psychiatric Rating Scale (BPRS): total, negative symptoms (NSs), positive symptoms (PSs), and anxietydepressive symptoms (ADSs). Time-relevant indices included age at the time of evaluation, age at the onset of psychosis, and duration of psychosis. The psychopathology of psychosis types and time-relevant indices were analyzed using Pearson's correlation coefficient analysis of covariance. Results: Age at the time of evaluation was significantly correlated with NS, and ADS scores. Age-relevant trajectories significantly interacted with psychosis types. As age advanced, patients with SC exhibited increased scores, whereas patients with CIIP often exhibited decreased (or unchanged) scores. Age at onset of psychosis was significantly correlated with NS and ADS outcomes in patients with CIIP, whereas it was not correlated in patients with SC. There were significant interactions between age at onset and psychosis types. Patients with early-onset CIIP exhibited higher NS and lower ADS scores, whereas patients with SC exhibited no particular trajectory. The duration of psychosis significantly interacted with the psychosis types in the BPRS total, NSs and PSs. As duration increased, patients with CIIP exhibited no significant relationship, whereas patients with SC exhibited significantly higher psychotic scores. Conclusion: Psychopathological courses differ between patients with CIIP and SC. Although patients with SC often exhibit deteriorations in psychotic symptoms, patients with CIIP exhibit no distinct deterioration. These findings can contribute psychiatric nosology, treatment strategies, and prediction outcomes.

Objectives: To clarify the pathophysiology of psychoses after the new administration of antiepileptic drugs (AED), we analyzed the annual incidence, timing of development, and duration of episodes. Methods: Psychotic outcomes in the first 6-month period after an AED or non-AED administration in patients with focal epilepsy were exhaustively reviewed in eight Japanese neuropsychiatry institutions. In cases with psychotic episodes, the subtype of psychosis, timing of development, previous history of psychosis, and duration of the episode were evaluated.Results: Between 1981 and 2015, 5018 new drugs (4402 AED and 616 non-AED) were administered to 2067 patients with focal epilepsy. In the first 6-month period, 105 psychotic episodes occurred (81 inter-ictal psychosis [IIP] and 24 postictal psychosis). Furthermore, 55 cases were first episodes and 50 were recurrent episodes. The frequency of psychoses is significantly higher after AED administration (n = 102) compared with non-AED administration (n = 3). Psychosis occurred most frequently in the ini-tial 1-month period after new-AED administration and tended to decrease with increasing time. The estimated annual incidence of all psychoses after a new AED administration was 3.5% (2.0% for first-episode psychosis and 1.8% for first-episode IIP). Duration of psychoses (mean, 38.5 weeks) was equivalent to overall IIP. Duration of IIP did not shorten with discontinuation of newly administered AED. Significance: Patients with epilepsy exhibit psychosis more frequently after new AED administration than after non-AED administration. This study shows the pathophysiology of psychoses after AED administra-tion with annual incidence, the timing of development, and the duration of PAP, which have rarely been reported.(c) 2023 Elsevier Inc. All rights reserved.

Objectives To evaluate cognitive functions including memory in middle-aged and elderly patients with antiseizure drug-naïve late-onset temporal lobe epilepsy (TLE). Methods We performed assessments with the Wechsler Adult Intelligence Scale-III (WAIS-III) and Wechsler Memory Scale-Revised (WMS-R) in 26 antiseizure drug-naïve patients with late-onset TLE, in comparison to 30 healthy subjects. We investigated the relationships between these cognitive function scores and clinical characteristics, seizure frequency, and frequency of interictal epileptic discharges (IEDs). Results Patients with epilepsy had a significantly lower score than healthy controls in the verbal intelligence quotient (IQ), the performance IQ, and full-scale IQ in intelligence testing. Patients showed significantly decrease in the verbal memory scores, visual memory scores, general memory scores, and delayed recall scores compared with those in the control subjects. Delayed recall scores were significantly negatively correlated with recent seizure frequency and the total IEDs count per minute, but not with age of onset or duration of illness. Significance Patients with antiseizure drug-naïve late-onset TLE displayed cognitive deficits including the domains of memory by using standard clinical neuropsychological test. Patients with late-onset epilepsy need to be considered for cognitive dysfunction at the time of diagnosis of TLE because they may have their daily life and work affected not only by epileptic seizures but also by cognitive deficits. Appearance of seizures and EEG abnormalities may affect the memory function in patients with late-onset TLE.

OBJECTIVE:There is a historical debate whether psychopathology of epilepsy psychosis is unique to epilepsy or common to other psychoses. However, a large comprehensive studies on this issue are scarce. To clarify the characteristics of interictal psychosis (IIP), we evaluated psychopathology quantitatively. METHODS:This study included 150 patients with IIP (epilepsy+/psychosis+), 187 patients with schizophrenia (SC: epilepsy-/psychosis+), 182 patients with epilepsy (EP: epilepsy+/psychosis-), and 172 non-clinical individuals (NC: epilepsy-/psychosis-). The IIP group comprised 127 chronic and 23 brief psychoses. Age, sex, and years of education, onset and duration of psychosis, and onset and duration of epilepsy were matched among the groups. The psychopathology was evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS), which comprises three symptom factors namely negative symptoms (NS), positive symptoms (PS), and anxiety-depressive symptoms (ADS). RESULTS:For overall 16-BPRS and NS factor scores, there were significant interactions between epilepsy-related (epilepsy+/-) and psychosis-general (psychosis+/-) effects. The EP exhibited higher scores than did the NC, whereas the IIP exhibited lower scores than did the SC. For PS and ADS factor scores, the IIP and SC exhibited a significant psychosis-general effect. Chronic IIP was associated with more serious psychopathologies than was brief IIP. However, limited with chronic IIP, there was a significant interaction between epilepsy-related and psychosis-general effects on the overall 16-BPRS and NS factor scores. CONCLUSION:These findings demonstrate the first large quantitative evidence on the unique psychopathology of IIP which has been only narratively described. The psychopathology is associated with the interaction between epilepsy-related and psychosis-general effects.

Background Psychosis often develops after the administration of antiepileptic drugs (AEDs) in patients with epilepsy. However, the individual vulnerability and clinical condition of such patients have been rarely scrutinised. We investigated the effect of individually consistent (trait-dependent) and inconsistent (state-dependent) characteristics. Methods The individual characteristics, clinical states and psychotic outcome of patients from eight adult epilepsy clinics were retrospectively reviewed over 6-month periods after a new drug (AED or non-AED) administration between 1981 and 2015. Results A total of 5018 new drugs (4402 AEDs and 616 non-AEDs) were used in 2015 patients with focal epilepsy. Subsequently, 105 psychotic episodes (81 interictal and 24 postictal) occurred in 89 patients. Twelve patients exhibited multiple episodes after different AED administrations. Trait-dependent characteristics (early onset of epilepsy, known presumed causes of epilepsy, lower intellectual function and a family history of psychosis) were significantly associated with the patients who exhibited psychosis. Absence of family history of epilepsy was also associated with psychosis but not significantly. Subsequent logistic regression analysis with a model incorporating family history of psychosis and epilepsy, and intellectual function was the most appropriate (p=0.000). State-dependent characteristics, including previous psychotic history and epilepsy-related variables (longer duration of epilepsy, AED administration, higher seizure frequency and concomitant use of AEDs) were significantly associated with psychotic episodes. Subsequent analysis found that a model including AED administration and previous psychotic history was the most appropriate (p=0.000). Conclusion Psychosis occurring after new AED administration was related to the individual vulnerability to psychosis and intractability of epilepsy.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees. A total of 143 participants, including 43 familial patients, 5 suspected patients, 3 sporadic nonfamilial patients, 22 unaffected familial members, and 70 unrelated controls, were screened for expanded abnormal pentanucleotide repeats in SAMD12, TNRC6A, RAPGEF2, YEAT2, MARCH6, and STARD7. DNA samples were analyzed using Southern blotting, long-range polymerase chain reaction (PCR), repeat-primed PCR, and long-range PCR followed by Southern blotting. Of the 51 individuals with clinically diagnosed or suspected BAFME, 49 carried a SAMD12 allele with an expanded TTTCA/TTTTA pentanucleotide repeat. Genetic and clinical anticipation was observed. As in previous reports, the one patient with homozygous mutant alleles showed more severe symptoms than the heterozygous carriers. In addition, screening for expanded pentanucleotide repeats in TNRC6A revealed that the frequency of expanded TTTTA repeat alleles in the BAFME group was significantly higher than in the control group. All patients who were clinically diagnosed with BAFME, including those in the original family reported by Yasuda, carried abnormally expanded TTTCA/TTTTA repeat alleles of SAMD12. Patients with BAFME also frequently carried a TTTTA repeat expansion in TNRC6A, suggesting that there may be unknown factors in the ancestry of patients with BAFME that make pentanucleotide repeats unstable.

OBJECTIVE:Many studies show psychoses after some antiepileptic drug (AED) administrations (post-AED administration psychoses [PAP]). It remains uncertain about psychogenetic potential of each AED and effects of clinical state factors on PAP. We examined the relations between AED-related factors (types, generations, dosages, and concomitant AED) and PAP.METHODS:The clinical records of patients with focal epilepsy were retrospectively reviewed from eight adult epilepsy clinics, for every six-month period after administration of a new drug (either AED or non-AED) between 1981 and 2015. Characteristics of psychotic episodes, AED-related factors (type, daily dosage, and concomitant AED), and other state-related risk factors to psychosis (age, duration of epilepsy, history of psychosis, and seizure frequency) were examined. Psychogenetic risks of AED-related and state-related factors were analyzed with multifactorial procedures.RESULTS:Of 2067 patients with focal epilepsy, 5018 new drugs (4402 AEDs and 616 non-AEDs) were administered. Within the first six-month period, 89 patients exhibited 105 psychotic episodes (81 interictal and 24 postictal psychoses: 55 first episodes and 50 recurrences). With second-generation AED (SAED) administration, particularly topiramate and lamotrigine, frequency of psychosis was significantly increased. Daily dosage of AED was not significantly associated with psychosis. Psychosis tended to occur with a higher number of concomitant AED. Subsequent analysis with AED-related and general factors showed that SAED administrations and previous psychotic history were the most significant risks for PAP.CONCLUSION:Post-AED administration psychoses is associated with type of AED (SAED), rather than its dosage. Individual vulnerabilities are also associated with PAP.

IMPORTANCE Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated. OBJECTIVE To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016. EXPOSURES Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. MAIN OUTCOMES AND MEASURES Incidence of carbamazepine-induced cADRs. RESULTS Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001). CONCLUSIONS AND RELEVANCE Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.

Objective Despite a theoretical consensus that interictal psychosis (IIP) is related to various epilepsy-related factors, the impact of seizure activity on development of IIP remains inconclusive. This is the first controlled study using quantitative seizure-activity measures at the onset of IIP. Methods One hundred and eighty-one patients with epilepsy who exhibited first-episode IIP (IIP group) and 427 patients with epilepsy without psychotic episodes (control group) were enrolled. The control group was matched for age, epilepsy type, and duration of epilepsy. The two seizure-activity indices (seizure frequency at the time of onset of first-episode IIP and the number of seizures before the onset of IIP) were evaluated and compared between the IIP and control groups. Logistic regression analysis was used for extracting risk variables to develop first-episode IIP. Results The sum of previous seizures was greater in the IIP than in control groups. This was particularly the case in the patients with partial epilepsies (PE). Higher seizure frequency in the patients with PE was associated with the development of first-episode IIP while no association was found in the whole cohort or in the patients with generalized epilepsies (GE). Subsequent multivariate analysis revealed the sum of previous seizures and family history of psychosis as risk variables to first-episode IIP. Conclusions The accumulation of seizure-related damages and family history of psychosis is associated with the onset of IIP episodes, particularly in the patients with PE. Seizure activity and individual vulnerability to psychosis are likely to be interacted for as the development of IIP in patients with epilepsy.

We encountered a female patient with late-onset temporal lobe epilepsy who presented with transient amnesia as the sole ictal manifestation, an accelerated rate of forgetting daily life events, and a retrograde memory deficit. We describe the memory function of the patient both before and after the administration of antiseizure medication. After the patient's seizures were controlled with antiseizure drugs, her neuropsychological memory performance scores showed improvement. We presumed that the disappearance of seizures was associated with a decrease in the accelerated rate of forgetting medication. However, her lost memories were not recovered after the seizures were controlled by antiseizure medication.

BACKGROUND AND PURPOSE:Automated subfield volumetry of hippocampus is desirable for use in temporal lobe epilepsy (TLE), but its utility has not been established. Automatic segmentation of hippocampal subfields (ASHS) and the new version of FreeSurfer software (ver.6.0) using high-resolution T2-weighted MR imaging are candidates for this volumetry. The aim of this study was to evaluate hippocampal subfields in TLE patients using ASHS as well as the old and new versions of FreeSurfer.MATERIALS AND METHODS:We recruited 50 consecutive unilateral TLE patients including 25 with hippocampal sclerosis (TLE-HS) and 25 without obvious etiology (TLE-nonHS). All patients and 45 healthy controls underwent high-resolution T2-weighted and 3D-volume T1-weighted MRI scanning. We analyzed all of their MR images by FreeSurfer ver.5.3, ver.6.0 and ASHS. For each subfield, normalized z-scores were calculated and compared among groups.RESULTS:In TLE-HS groups, ASHS and FreeSurfer ver.6.0 revealed maximal z-scores in ipsilateral cornu ammonis (CA) 1, CA4 and dentate gyrus (DG), whereas in FreeSurfer ver.5.3 ipsilateral subiculum showed maximal z-scores. In TLE-nonHS group, there was no significant volume reduction by either ASHS or FreeSurfer.CONCLUSIONS:ASHS and the new version of FreeSurfer may have an advantage in compatibility with existing histopathological knowledge in TLE patients with HS compared to the old version of FreeSurfer (ver.5.3), although further investigations with pathological findings and/or surgical outcomes are desirable.

Psychogenic nonepileptic seizures (PNESs) in patients with epilepsy can be categorized as dissociative disorders. The prevalence of PNESs in patients with epilepsy appears to be much higher than that of dissociative experiences in nonclinical subjects. In order to clarify as to whether epilepsy-related factors were associated with pathological dissociation, we conducted a controlled study with 225 patients with epilepsy and 334 nonclinically matched individuals. All participants completed the Japanese version of the Dissociative Experiences Scale (DES). There was no significant difference in the DES score (DES-S) between the group with epilepsy and the control group. The group with epilepsy showed a significantly higher DES taxon (DES-T; a subset of DES-S and an index of pathological dissociation) than the control group. Thirty-one out of the 225 patients with epilepsy (13.8%) had PNESs. Because of its strong association with the DES-S and DES-T, PNESs can be regarded as a symptom of dissociation. With multiple regression analysis, the patients with a shorter duration of epilepsy, higher seizure frequency, or shorter period in education tend to suffer from pathological dissociation. These findings demonstrate that patients with epilepsy are more prone to experiencing pathological dissociation when having certain clinical factors.

Benign adult familial myoclonus epilepsy (BAFME) is an autosomal dominant disease characterized by cortical tremor and infrequent generalized seizures. We aimed to clarify the generator mechanism of cortical tremor in BAFME by means of corticomuscular coherence. We employed 15 patients with BAFME diagnosed based on clinical and electrophysiological findings. EEG, EMG and accelerometer were simultaneously recorded in all 15 patients. Among them, in addition, magnetoencephalography (MEG), EEG and EMG were also simultaneously recorded on different occasions in 3 patients. Patients were instructed to keep the hand in the outstretched posture with and without loading weight on the hand. We compared the power spectrum among tasks to judge whether the tremor was presumably of cerebral or peripheral origin. As the results, the frequency band showing significant corticomuscular coherence matched that of peak power spectrum of cortical tremor only in 3 patients. On the other hand, they differed in the remaining 12 patients. Thus, the cortical tremor in BAFME could not be initiated or regulated directly by cerebral cortex but possibly by other structures such as subcortical or cerebellum structures, like those responsible for essential tremor.

Controversy exists regarding the similarity between depression as seen in patients with epilepsy and in those with idiopathic major depression. The objective of this study was to examine whether anger is a distinctive feature of depression in epilepsy. Participants included 487 adult patients with epilepsy (study group) and 85 patients with idiopathic major depression according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria, and without other neurological complications (control group). All participants completed the Inventory of Depressive Symptomatology Self-Report (IDS-SR) and the Buss-Perry Aggression Questionnaire (BAQ). The IDS-SR is a self-report questionnaire that measures depression severity and assesses all symptoms of depression as defined by the DSM-IV. The BAQ is a self-rating scale designed for assessing aggression. After examining potential confounding factors (i.e., demographic and clinical variables) using a multivariate linear regression model, BAQ scores were compared between the study (n = 85) and control groups (n = 54) for patients with moderate or severe depression using established cut-off points (IDS-SR score > 25). BAQ scores were significantly higher in the study group (P = 0.009). Among the BAQ subscales, only anger showed a statistically significant difference (P = 0.013). Although a significant correlation was revealed between the IDS-SR and BAQ scores in the study group, no such correlation was found in the control group. Thus, anger might be a constituent component of depression among epilepsy patients, but not among idiopathic major depression patients.

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions.

Classic antidepressants have been known to induce convulsive seizures and nonconvulsive status epilepticus (NCSE). On the other hand, many reports have emphasized the safety of novel antidepressants. However, we encountered three cases of NCSE in the elderly associated with the use of newer antidepressants at therapeutic doses. All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each), impaired consciousness appeared. Electroencephalography (EEG) showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

Treatment protocols for interictal psychosis (IIP) of patients with epilepsy have not yet been established. We aimed to clarify the effects of antipsychotic drugs (APDs) on duration of IIP episodes. We studied 393 IIP episodes in 200 patients with epilepsy in accordance with our empirical treatment protocol. The duration of all the episodes and APD treatments were reviewed. Antipsychotic drugs were used in 338 episodes and not used in 55 episodes (non-APD group). The APDs used in the treatment of IIP episodes were divided into the following three groups: first-generation APDs (FAPD, n=252), second-generation APDs (SAPD, n=44), and the combination of first- and second-generation APDs (CAPD, n=42). The non-APD group showed a significantly shorter episode duration than did the APD group (F=6.05, p=0.014). Among the 3 APD groups (FAPD, SAPD, and CAPD), there was a significant difference in duration of IIP episode (F=8.65, p=0.000). Whereas the duration of episodes was significantly longer in the CAPD group than in the other two groups, it was not significantly different between the FAPD and SAPD groups. Our findings further to clarify the nature of IIP and add further perspectives on treatment protocols for IIP.

Purpose: There have been few reports showing the distribution of the duration of interictal psychosis (IIP) episodes and their association with clinical characteristics. To clarify the nature of IIP, we studied the duration of IIP episodes and their related factors. Methods: One hundred fifty-five patients with epilepsy exhibited 320 IIP episodes during our follow-up period (mean 16.9 years). The duration of all the episodes and the longest episode in each patient during the follow-up periods were studied. Characteristics of the patients (e.g., epilepsy type, age of onset, and family history of psychosis) and episode-specific factors (e.g., age of the episode, seizure frequency, administrations of antiepileptic drugs [AEDs] and antipsychotic drugs [APDs]) were analyzed in association with the duration of the episodes. Key Findings: Mean duration of the 320 IIP episodes was 82.7 weeks and that of the longest IIP episodes was 150.1 weeks. During the follow-up period, 17 patients (11.0%) showed all episodes remitting within a month and 54 (34.8%) showed all episodes lasting for 6 months or longer. The IIP episodes that occurred at a younger age were often prolonged. Patients with a family history of psychosis or with early onset of psychosis tended to have more prolonged IIP episodes. Among the episodes treated with APDs, early administration of APDs was significantly associated with shorter IIP duration. Significance: The distribution of the duration of IIP episodes indicated the broad spectrum and heterogeneity of the IIP phenomena. The individual vulnerability to psychosis may be associated with prolonged episodes. Administration of APDs soon after onset of the episodes appeared to be effective in controlling them. These findings support empirical treatment principles for IIP to administer APDs at an early stage of its development.